Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Autochthonous borderline tuberculoid leprosy in a man from Florida.

Leprosy (Hansen's disease) is a chronic contagious granulomatous disease principally affecting the skin and peripheral nervous system, caused by Mycobacterium leprae. In this report, we present a case of autochthonous leprosy in a man from Florida as the first human case reported from this region. Authors believe dermatologists need to be aware of the possibility of autochthonous transmission of leprosy in the Eastern-Southern United States, and should consider leprosy in any patient with atypical skin lesions, even when a history of contact with armadillo is missing.

Limitations of clinico-histopathological correlation of skin biopsies in leprosy.

BACKGROUND: Skin biopsies play an important role in diagnosing and classifying different types of leprosy. The aim of this study was to analyse different histologic types of leprosy, to correlate histopathological diagnosis with clinical diagnosis, to study the uniformity of clinical and histological findings in the diagnosis of leprosy and to evaluate difficulties faced during clinicopathological correlation according to Ridley- Jopling classification due to inadequacy of data provided. METHODS: This is a retrospective study of all skin biopsies reported from Department of Pathology of Tribhuvan University Teaching Hospital from 14 April 2007 to 13 April 2009, for which leprosy was the diagnosis or was strongly suspected on histopathology. RESULTS: Out of 40 cases included, 33 were males and seven were females. Tuberculoid leprosy was the most common type comprising 23 /40 cases (57.5%). In 18/ 40 cases (45%), clinical diagnosis was leprosy. Only in three, leprosy was classified according to Ridley-Jopling criteria clinically. Thus clinicopathological correlation according to Ridley-Jopling criteria could not be done. Histopathological reporting lacked uniformity too. In 13/40 reports (32.5%), exact location of granuloma, presence or absence of Grenz zone and enroachment of epidermis by granuloma was not mentioned. None mentioned the number and distribution of lymphocytes or relative proportion of epithelioid cells and foamy histiocytes. Results: Out of 40 cases included, 33 were males and seven were females. Tuberculoid leprosy was the most common type comprising 23 /40 cases (57.5%). In 18/ 40 cases (45%), clinical diagnosis was leprosy. Only in three, leprosy was classified according to Ridley-Jopling criteria clinically. Thus clinicopathological correlation according to Ridley-Jopling criteria could not be done. Histopathological reporting lacked uniformity too. In 13/40 reports (32.5%), exact location of granuloma, presence or absence of Grenz zone and enroachment of epidermis by granuloma was not mentioned. None mentioned the number and distribution of lymphocytes or relative proportion of epithelioid cells and foamy histiocytes. CONCLUSIONS: Histopathological diagnosis of leprosy did not correlated with clinical diagnosis significantly. Uniformity was not seen in the clinical or histopathological informations provided making it difficult to conduct retrospective clinico pathological correlation.

Histopathological lesions of apparently normal skin in leprosy patients.

This study was carried out on 50 patients with different clinical types of leprosy 38 males (76 % and 12 females (24%), ages ranged from 14 -70 years with a mean age +/- SD 49.22 +/- 12.97 years. Mean disease duration was 5.65 years +/- SD = 9.27 selected to study a group of leprosy patients and compare the clinical parameters with histopathological findings and bacteriologic status of the skin to evaluate the relevance of their patients. Patients were subjected to full medical history taking including disease duration, type and duration of previous or current therapies. Complete clinical examination, for the determination of the clinical type of leprosy. Skin slit smear (SSS) and skin biopsies were taken and examined after staining for histopathological assessment and Acid fast bacilli (AFB). SPSS package version (statistical Package for Social Sciences) was used for data analysis. The biopsy of normally looking skin showed classic histopathological features of leprosy in more than half of the cases (26 cases, 52%). The histopathological types of leprosy diagnosed in such cases were as follows: indeterminate leprosy (IL) in 4 cases (15.38%), Tuberculoid leprosy (TL) in 2 cases (7.69%), Borderline tuberculoid (BT) in 4 cases (15.38), Borderline Borderline (BB) i.e Query in 8 cases (30.76%), Borderline Lepromatous (BL) in 7 cases (26.92%) and Lepromatous leprosy (LL) in a patient (3.84%). Other 24 cases showed either no evidence of leprosy in (9 cases, 37.5%), or query findings (in the form of sweat gland changes either alone or in combination with thickened nerves and superficial and deep perivascular lymphohistiocytic infiltrate) in 15 cases (62.5%). Histopathology of skin lesion biopsies showed TL in 3 cases (6%), BT in 8 cases (16%), BB in 8 cases (16%), BL in 14 cases (28%), LL in 12 cases (24%) and leprosy in reaction in 5 cases (10%). In 16 cases (32%), histopathological type of leprosy detected by microscopical examination of biopsies from skin lesions differed from that diagnosed by clinical examination.

Use of protein microarrays to define the humoral immune response in leprosy patients and identification of disease-state-specific antigenic profiles.

Although the global prevalence of leprosy has decreased over the last few decades due to an effective multidrug regimen, large numbers of new cases are still being reported, raising questions as to the ability to identify patients likely to spread disease and the effects of chemotherapy on the overall incidence of leprosy. This can partially be attributed to the lack of diagnostic markers for different clinical states of the disease and the consequent implementation of differential, optimal drug therapeutic strategies. Accordingly, comparative bioinformatics and Mycobacterium leprae protein microarrays were applied to investigate whether leprosy patients with different clinical forms of the disease can be categorized based on differential humoral immune response patterns. Evaluation of sera from 20 clinically diagnosed leprosy patients using native protein and recombinant protein microarrays revealed unique disease-specific, humoral reactivity patterns. Statistical analysis of the serological patterns yielded distinct groups that correlated with phenolic glycolipid I reactivity and clinical diagnosis, thus demonstrating that leprosy patients, including those diagnosed with the paucibacillary, tuberculoid form of disease, can be classified based on humoral reactivity to a subset of M. leprae protein antigens produced in recombinant form.

An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of fixed duration therapy.

The present study was carried out involving 25 patients with paucibacillary leprosy who attended the outpatient department of dermatology of Father Muller's Medical College Hospital during the period January 2001 to March 2002. All the patients were examined clinically and histopathologically at the beginning and at the end of six months of MDT and relevant data recorded. Clinicopathological correlation with histopathological classification before MDT was 72% and 68% at the end of MDT in our study. At the end of treatment 4 (16%) cases were clinically active and 8 (32%) were histopathologlcally active. The study showed that active cases were significantly reduced as a result of MDT, both clinically and histopathologically. The histopathological activity that outlasts MDT may be due to the bacillary fragments that persist; but clinical activity coupled with histopathological activity seen in 2 patients at the end of 6 months of MDT was possibly an indicator of relapse and these patients and similar others need to be followed up for a longer duration. In this study, resolution of granuloma and clinical activity after completion of MDT were assessed.

Use of genetic profiling in leprosy to discriminate clinical forms of the disease.

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Use of genetic profiling in leprosy to discriminate clinical forms of the disease

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Prevalencia de olho seco em portadores de hanseniase do Hospital de Dermatologia Sanitaria de Goiania / ?

Objetico: Determinar a prevalencia de olho seco em portadores de hanseniase do Hospital de Dermatologia Sanitaria de Goiania, comparando-se a um grupo controle. Desenho: Estudo de prevalencia. Material e metodos: A amostra do presente estudo inclui 70 portadores de hanseniase, do Hospital de Dermatologia Sanitaria de Goiania, e 30 individuos no grupo controle, da Fundacao Banco de Olhos de Goias, ambos localizados em Goiania-GO. Foram realizados exeme oftalmologico e testes de Schirmer I, break-up time (BUT) e rosa bengala em todos estes individuos em uma unica avaliacao. Resultados: Quarenta e quatro (63,0%) portadores de hanseniase eram do sexo masculino e 22 73,3%) individuos do grupo controle, do sexo feminino (p=0,001). A idade medica dos hansenianos foi de 61,1+-12,5 anos e no grupo controle, 55,7+-9,6 anos. Quinze (21,4%) hansenianos e quatro (13,3%) individuos deo grupo controle apresentaram diagnostico de olho seco (p=0,429) A forma virchowiana (74,2%) da hanseniase foi a mais prevalente e o olho seco (66,7%) foi mais frequente nesta forma clinica da doenca. Conclusao: A prevalencia de olho seco nos portadores de hanseniase foi semelhante a encontrada nos individuos do grupo controle

Utility of fine-needle aspiration cytology in the classification of leprosy.

The role of fine-needle aspiration cytology (FNAC) in the diagnosis of benign skin lesions has been restricted primarily to the evaluation of bacteriologic and morphologic indices in leprosy. This study was undertaken to evaluate the efficacy of FNAC in the diagnosis and classification of lepromatous lesions. Aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial load was determined by modified Ziehl-Neelsen (ZN) stain. A skin biopsy was taken from the same site at the same sitting. Frozen and paraffin sections stained with hematoxylin-eosin (H&E) and ZN stains were examined from the biopsy specimen. In 61 of 94 cases (64.9%), the aspirates were satisfactory. Both diagnosis and classification of leprosy were possible in 40 of these 61 cases; the rest of the aspirates showed nonspecific chronic inflammation. The 39 cases of leprosy where a biopsy was available from the same site were classified on FNAC into tuberculoid (TT and BT), lepromatous (LL and BL), and midborderline (BB) subtypes. Taking the histologic diagnosis and Ridley-Jopling classification to be the gold standard, a strong concordance in tuberculoid leprosy cases (18 of 20 cases, 90%) and in lepromatous cases (15 of 16 cases, 93.7%) was observed. Midborderline cases of leprosy posed a problem, and a correct cytohistological correlation was observed in only one of the three cases.

Histological changes in the nerve, skin and nasal mucosa of patients with primary neuritic leprosy.

Primary neuritic leprosy (PNL) presents as a peripheral neuropathy with no visible skin patches and skin smears negative for acid fast bacilli. The pathogenesis of PNL is poorly understood. The aim of the study was to document the histological changes in the nerve, apparently normal skin and nasal mucosa in PNL and to study its significance to the pathogenesis of leprosy lesions. The study is based on a cohort of 208 PNL patients registered at the Schieffelin Leprosy Research and Training Centre, Karigiri. All patients had a nerve biopsy, 196 had a skin biopsy and 39 had a nasal mucosal biopsy. The findings reveal that PNL patients exhibit a spectrum of disease histologically in the nerve ranging from lepromatous to tuberculoid leprosy with a significant proportion (46%) manifesting a multibacillary leprosy histology. Findings in the apparently normal skin and nasal mucosa reveal that there are widespread changes due to leprosy in tissues such as the skin and nasal mucosa even when the disease appears clinically confined to a few nerves. PNL may be an early stage in the pathogenesis of the disease before the appearance of skin lesions. The number of nerves enlarged and lepromin status did not give any clue to the nature of underlying disease.

Leprosy among inmates of a prison.

A leprosy survey carried out in a district prison revealed a gross prevalence of 20 cases per 1000, and active prevalence of 10 cases per 1000 whereas, prevalence of leprosy in the state was 1.12 per 1000. Such prisons thus form hyperendemic pockets. The inmates are a closed community and there is a risk of cases among inmates spreading infection to others inside the prison during their sojourn there and to the community when they are released from the prison. Special efforts are required to identify and eliminate all identifiable sources of infection, especially at this point of time when we are aiming at elimination of leprosy as a public health problem.

A clinico-pathological study of macular lesions in leprosy.

One hundred twenty histologically confirmed cases of leprosy having macular lesions were evaluated clinically and histopathologically according to Ridley-Jopling classification. Of these 120 cases, the majority (91 or 75.8%) were young adults. The main clinical findings were: a single macule in 42 patients (35%), multiple macules 2-5 in numbers in 35 patients (29.1%), 6-10 macules in 17 patients (14.1%) and more than 10 macules in 26 patients (21.6%). Impairment of sensation over the macular lesions was present in 62 cases (51.6%), total loss of sensation was noticed in 31 patients (25.8%) and sensation was intact in 27 patients (22.5%). Acid-fast bacilli were detected in 11 cases (9.1%) by slit-skin smear examination. Clinical examination of the 120 cases revealed features of TT in 16 (13.3%), BT in 41 (34.1%), BB in 11 (9.1%), BL in 13 (10.8%), LL in 7 (5.8%) and indeterminate leprosy (IL) in 32 patients (26.6%). On the contrary, histologically there were 22 cases of TT (18.3%), 38 cases of BT (31.6%), 8 (6.5%) BB, 10 BL (8.3%), 7 LL (5.8%) and 35 cases of IL (29.1%). Histopathological features were consistent with the clinical picture in 84 patients (70%).